Apnea and oxygen instability in preterm infants

The fetal to neonatal transition is physiologically demanding for the preterm neonate. This transition requires rapid coordination of an immature respiratory control system with recruitment of underdeveloped lungs to initiate and achieve effective pulmonary ventilation. As a result, respiratory instability is common in preterm infants during early postnatal life with profiles of apnea and periodic breathing characterized by a sharp rise in incidence during the first postnatal weeks, followed by a gradual decline thereafter. The frequency of these events is inversely correlated with gestation age. A major consequence of apnea and periodic breathing is the accompanying intermittent hypoxemia which has been associated with numerous life-long developmental sequelae. Current treatment modalities including pressure support, supplemental oxygen and pharmacological interventions reduce but do not totally resolve apnea, periodic breathing, or intermittent hypoxemia events. Therefore, the purpose of this review is to compile some of the key clinical data related to respiratory system development to build associations between modulators of respiratory control (e.g. neurotransmitter development) and how they could contribute to the generation of apnea, periodic breathing, and intermittent hypoxemia during postnatal life. We hope these data shed light into potential mechanisms of apnea and periodic breathing in the hope of stimulating insight into our understanding of their origins, and how they may lead to future therapeutics to prevent lifelong developmental sequelae.